Review articles

By Prof. Nadeem Siddiqui , Mr. M Shamsher Alam , Dr. Ozair Alam , Ms. Andalip , Mr. Bishmillah Azad
Corresponding Author Prof. Nadeem Siddiqui
Department of Pharmaceutical Chemistry, Jamia Hamdard, INDIA, - India 110062
Submitting Author Prof. Nadeem . Siddiqui
Other Authors Mr. M Shamsher Alam
Department of Pharmaceutical Chemistry, Jamia Hamdard, INDIA, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi-62,INDIA - India 110062

Dr. Ozair Alam
Department of Pharmaceutical Chemistry, Jamia Hamdard, INDIA, Department of Pharmaceutical Chemistry,Faculty of Pharmacy, Jamia Hamdard, New Delhi-62,INDIA - India 110062

Ms. Andalip
Department of Pharmaceutical Chemistry, Jamia Hamdard, INDIA, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi-62,INDIA - India 110062

Mr. Bishmillah Azad
Department of Pharmaceutical Chemistry, Jamia Hamdard, INDIA, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi-62, INDIA - India 110062


Fluoxetine, Molecular Modelling, Mode of Action

Siddiqui N, Alam M, Alam O, A, Azad B. Fluoxetine: Pharmacological and Computational Study. WebmedCentral PHARMACEUTICAL SCIENCES 2011;2(3):WMC001800
doi: 10.9754/journal.wmc.2011.001800
Submitted on: 23 Mar 2011 11:10:27 AM GMT
Published on: 24 Mar 2011 08:37:53 PM GMT


Major depressive disorder is currently the fourth leading cause of disease or disability worldwide. Fluoxetine is approved for the treatment of major depression (including paediatric depression), obsessive-compulsive disorder (in both adult and paediatric populations), bulimia nervosa, panic disorder and premenstrual dysphoric disorder. Compared to other popular Selective Serotonin Reuptake Inhibitors (SSRIs), fluoxetine has a strong energizing effect. The study shows fluoxetine is effective in the treatment of depression. The pharmacological and computational studies have been presented.


Depression is a chronic, recurring and potentially life threatening illness that affects up to 20% of the population worldwide. It is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being1. The report summarizes the results of that analysis, which indicated that, among 235,067 adults (in 45 states, the District of Columbia [DC], Puerto Rico, and the U.S. Virgin Islands), 9.0% met the criteria for current depression, including 3.4% who met the criteria for major depression. By state, age-standardized estimates for current depression ranged from 4.8% in North Dakota to 14.8% in Mississippi.2 A review of all studies of anti-depressants ever submitted to the U.S. Food and Drug Administration (FDA), published and unpublished, was submitted to the FDA in 2004. In the published literature, anti-depressants had 94% success in treating depression.3,4 Recent advancement in antidepressant therapeutics included the monoamine oxidase inhibitors (MAOIs, e.g. Nardil) tricyclic antidepressants (TCAs, e.g. Elavil), serotonin selective reuptake inhibitor (SSRI) (Prozac), inhibition of serotonin reuptake transporter (SERT), norepinephrine reuptake inhibitors (NRIs). Anxiety disorders, such as post–traumatic stress disorder (PTSD), obsessive–compulsive disorder, panic disorder, social phobia and generalized anxiety disorder, often accompany depression.5,6  In a National Institute of Mental Health (NIMH)–funded study, researchers found that more than 40 percent of people with PTSD also had depression at one-month and four-month intervals after the traumatic event.7 Alcohol and other substance abuse or dependence may also co–occur with depression. The higher doses of fluoxetine appeared to result in better response, while the reverse relationship was observed in the treatment of depression.8 Fluoxetine has been approved by the FDA for the treatment of major depression, obsessive compulsive disorder, bulimia nervosa and panic disorder.8
In fact, research has indicated that the co–existence of mood disorders and substance abuse is pervasive among the U.S. population.9 Fluoxetine is Over 22.2 million prescriptions for generic formulations of fluoxetine were filled in the United States,  making it the third most prescribed antidepressant after sertraline (SSRI that became generic in 2006) and escitalopram (non-generic SSRI).Consequently, there is still a great need for faster acting, safer, and more effective treatments for depression. The present review focuses on the pharmacological and computational approach to establish fluoxetine is good candidate for antidepressant treatment.

Mode of Action

Fluoxetine is selective serotonin reuptake inhibitor; it worked by inhibiting the uptake of serotonin by the neurons in the brain and enhances serotonin neurotransmission through action on 5HT2ain particular 5HT2c receptors. It has longest half-life in all the selective serotonin reuptake inhibitors (SSRIs); it may also produce some of its effects through 5-HT2C antagonism10. Fluoxetine does not significantly inhibit nor epinephrine and dopamine reuptake.


The bioavailability of fluoxetine is relatively high (72%), and peak plasma concentrations are reached in 6 to 8 hours. It is highly bound to plasma proteins, mostly albumin. Fluoxetine is well absorbed from the gastrointestinal tract. After oral administration peak plasma concentration occurs between 4-8 or 6-12 h and maximal cerebral effect reported between 8-10 h. Fluoxetine undergoes hepatic metabolism and CYP2D6 isoenzyme convert fluoxetine to pharmacologically active metabolite norfluoxetine by demethylation, norfluoxetine is also serotonin reuptake blocker.11 Fluoxetine has a long Tl/2 of 1-3 days after a single dose or 2-7 days after repeated administration, while norfluoxetine has a TI/2 of approximately 7-15 days. Fluoxetine's excreted through urine and faeces. Fluoxetine is highly bound to plasma protein, with no displacement from plasma binding by lithium salts, warfarin, or digoxin, and little by ibuprofen.

Indication and Usage

The recent research suggests that a significant part of the resistance to the SSRIs paroxetine (Paxil) and citalopram (Celexa) can be explained by the genetic variation of Pgp transporter. Paroxetine and citalopram, which are Pgp substrates, are actively transported from the brain by this protein. Fluoxetine is not a substrate of Pgp, and thus a switch from paroxetine or citalopram to fluoxetine may be beneficial to the nonresponders.12, 13 Fluoxetine and its metabolite product norfluoxetine is used for treating depression (20-80 mg of fluoxetine daily), bulimia (60 mg of fluoxetine daily), obsessive-compulsive disorder (OCD) (20-60 mg daily), panic disorder (10-60 mg daily), and premenstrual dysphoric disorder (PMDD) (20 mg administered every day of the menstrual cycle or daily for 14 days prior to the onset of menstruation through the first day of menses). Combination with olanzapine (Zyprexa) is used for resistant depression and treatment of depression associated with bipolar disorder (20-50 mg fluoxetine and 5-12.5 mg olanzapine once daily in the evening).

Adverse Effects

Among the common adverse effects associated with fluoxetine, the effects with the greatest difference from placebo are nausea, insomnia, somnolence, anorexia, anxiety, nervousness, asthenia  and tremor Those that most often resulted in interruption of the treatment were anxiety, insomnia, and nervousness (1-2% each), and in pediatric trials—mania (2%).14 Similarly to other SSRIs, sexual side effects are common with fluoxetine; they include anorgasmia and reduced libido.

Computational analyses

Crystal data and physicochemical parameters of Fluoxetine have been presented in Table 1 and Table 2.


Fluoxetine has been approved by the FDA for the treatment of major depression, obsessive compulsive disorder, bulimia nervosa and panic disorder. The present study revealed that Fluoxetine with minimal side effects emerged as choice of drug among the antidepressants.


1. Salmans S. Depression: questions you have - answers you need. People's Medical Society. 1997, ISBN 9781882606146.
2. "Current Depression Among Adults --- United States, 2006 and 2008" Morbidity and Mortality Weekly Report (MMWR) October 1, 2010, 59(38): 1229-1235.
3. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. "Selective publication of antidepressant trials and its influence on apparent efficacy". N. Engl. J. Med. 2008, 358 (3): 252–260.
4. Joanna M, Simon W, Rebecca H, Joanna M. "Active placebos versus antidepressants for depression". Cochrane database of systematic reviews (Online) 2004, 1: CD003012. doi:10.1002/14651858.
5. Regier DA, Rae DS, Narrow WE, Kaebler CT, Schatzberg AF. Prevalence of anxiety disorders and their comorbidity with mood and addictive disorders. B. J. Psych. 1998, 173 (34): 24-28.
6. Devane CL, Chiao E, Franklin M, Kruep EJ. Anxiety disorders in the 21st century: status, challenges, opportunities, and comorbidity with depression. Am. J. Man. Care. 2005, 11 (12): S 344-353.
7. Shalev AY, Freedman S, Perry T, Brandes D, Sahar T, Orr SP, Pitman RK. Prospective study of posttraumatic stress disorder and depression following trauma. Am.  J. Psych. 1998, 155(5): 630-637.
8. "Prozac prescribing information" (PDF). Eli Lilly. 2007-06-21. Retrieved 2008-01-09.
9. Conway KP, ComptonW, Stinson FS, Grant BF. Lifetime comorbidity of DSM-IV mood and anxiety disorders and specific drug use disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J  Clin. Psych. 2006, 67(2): 247-257.
10. Ni YG, Miledi R. Blockage of 5HT2C serotonin receptors by fluoxetine (Prozac). Proc. Natl. Acad. Sci. U S A 1997, 4, 94(5): 2036-2040.
11. Prozac Pharmacology, Pharmacokinetics,Studies, Metabolism". 2007. Retrieved 2007-04-14.
12. Uhr M, Tontsch A, Namendorf C, Ripke S, Lucae S, Ising M, Dose T, Ebinger M, Rosenhagen M, Kohli M, Kloiber S, Salyakina D, Bettecken T, Specht M, Pütz B, Binder EB, Müller-Myhsok B, Holsboer F. "Polymorphisms in the Drug Transporter Gene ABCB1 Predict Antidepressant Treatment Response in Depression". Neuron. 2008, 57(2):203–209.
13. Kato M, Fukuda T, Serretti A, Wakeno M, Okugawa G, Ikenaga Y, Hosoi Y, Takekita Y, Mandelli L, Azuma J, Kinoshita T (). "ABCB1 (MDR1) gene polymorphisms are associated with the clinical response to paroxetine in patients with major depressive disorder". Prog. Neuropsychopharmacol. Biol. Psychiatry. 2008, 32(2): 398–404.
14. Settle EC, Settle GP. "A case of mania associated with fluoxetine". American Journal of Psychiatry 1984, 2: 141-144.

Source(s) of Funding


Competing Interests

Authors have no any conflict of interest in the given study.


This article has been downloaded from WebmedCentral. With our unique author driven post publication peer review, contents posted on this web portal do not undergo any prepublication peer or editorial review. It is completely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscript but also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions before submitting any information that requires obtaining a consent or approval from a third party. Authors should also ensure not to submit any information which they do not have the copyright of or of which they have transferred the copyrights to a third party.
Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater to the needs of an individual patient. The web portal or any content(s) therein is neither designed to support, nor replace, the relationship that exists between a patient/site visitor and his/her physician. Your use of the WebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harm that you may suffer or inflict on a third person by following the contents of this website.

0 comments posted so far

Please use this functionality to flag objectionable, inappropriate, inaccurate, and offensive content to WebmedCentral Team and the authors.


Author Comments
0 comments posted so far


What is article Popularity?

Article popularity is calculated by considering the scores: age of the article
Popularity = (P - 1) / (T + 2)^1.5
P : points is the sum of individual scores, which includes article Views, Downloads, Reviews, Comments and their weightage

Scores   Weightage
Views Points X 1
Download Points X 2
Comment Points X 5
Review Points X 10
Points= sum(Views Points + Download Points + Comment Points + Review Points)
T : time since submission in hours.
P is subtracted by 1 to negate submitter's vote.
Age factor is (time since submission in hours plus two) to the power of 1.5.factor.

How Article Quality Works?

For each article Authors/Readers, Reviewers and WMC Editors can review/rate the articles. These ratings are used to determine Feedback Scores.

In most cases, article receive ratings in the range of 0 to 10. We calculate average of all the ratings and consider it as article quality.

Quality=Average(Authors/Readers Ratings + Reviewers Ratings + WMC Editor Ratings)